@article{db68cf37cf1a46118e748b22dc18ae5e,
title = "Piwi–piRNA complexes induce stepwise changes in nuclear architecture at target loci",
abstract = "PIWI-interacting RNAs (piRNAs) are germline-specific small RNAs that form effector complexes with PIWI proteins (Piwi–piRNA complexes) and play critical roles for preserving genomic integrity by repressing transposable elements (TEs). Drosophila Piwi transcriptionally silences specific targets through heterochromatin formation and increases histone H3K9 methylation (H3K9me3) and histone H1 deposition at these loci, with nuclear RNA export factor variant Nxf2 serving as a co-factor. Using ChEP and DamID-seq, we now uncover a Piwi/Nxf2-dependent target association with nuclear lamins. Hi-C analysis of Piwi or Nxf2-depleted cells reveals decreased intra-TAD and increased inter-TAD interactions in regions harboring Piwi–piRNA target TEs. Using a forced tethering system, we analyze the functional effects of Piwi–piRNA/Nxf2-mediated recruitment of piRNA target regions to the nuclear periphery. Removal of active histone marks is followed by transcriptional silencing, chromatin conformational changes, and H3K9me3 and H1 association. Our data show that the Piwi–piRNA pathway can induce stepwise changes in nuclear architecture and chromatin state at target loci for transcriptional silencing.",
keywords = "RNA silencing, chromatin conformation, heterochromatin formation, nuclear localization, transcriptional regulation",
author = "Iwasaki, {Yuka W.} and Sira Sriswasdi and Yasuha Kinugasa and Jun Adachi and Yasunori Horikoshi and Aoi Shibuya and Wataru Iwasaki and Satoshi Tashiro and Takeshi Tomonaga and Haruhiko Siomi",
note = "Funding Information: We thank Shinsuke Shibata, Tomoko Shindo, Kensaku Murano, and Chikara Takeuchi for experimental support and Masaru Ariura for support and discussion on bioinformatic analyses. We also grateful to Dr. Bas van Steensel for sharing platforms for DamID experiments. We thank all the members of the Siomi laboratory, especially Hirotsugu Ishizu and Akihiko Sakashita for critical reading of the manuscript. Life Science Editors provided editing support on the manuscript. This work was supported by funding from JSPS KAKENHI Grant Numbers 19H05268 and 18H02421, JST PRESTO Grant Number JPMJPR20E2, The Uehara Memorial Foundation, Takeda Science Foundation, and The Nakajima Foundation to Y.W.I.; from JSPS KAKENHI Grant Number 19K23725 to Y.K.; from JSPS KAKENHI Grant Numbers 16H06279 and 19H04853 to W.I.; from JST CREST Grant Number JPMJCR18S3 to S.T.; and from JSPS KAKENHI Grant Number 19H05753 to H.S. Funding Information: We thank Shinsuke Shibata, Tomoko Shindo, Kensaku Murano, and Chikara Takeuchi for experimental support and Masaru Ariura for support and discussion on bioinformatic analyses. We also grateful to Dr. Bas van Steensel for sharing platforms for DamID experiments. We thank all the members of the Siomi laboratory, especially Hirotsugu Ishizu and Akihiko Sakashita for critical reading of the manuscript. Life Science Editors provided editing support on the manuscript. This work was supported by funding from JSPS KAKENHI Grant Numbers 19H05268 and 18H02421, JST PRESTO Grant Number JPMJPR20E2, The Uehara Memorial Foundation, Takeda Science Foundation, and The Nakajima Foundation to Y.W.I.; from JSPS KAKENHI Grant Number 19K23725 to Y.K.; from JSPS KAKENHI Grant Numbers 16H06279 and 19H04853 to W.I.; from JST CREST Grant Number JPMJCR18S3 to S.T.; and from JSPS KAKENHI Grant Number 19H05753 to H.S. Publisher Copyright: {\textcopyright} 2021 The Authors. Published under the terms of the CC BY 4.0 license",
year = "2021",
month = sep,
day = "15",
doi = "10.15252/embj.2021108345",
language = "English",
volume = "40",
journal = "EMBO Journal",
issn = "0261-4189",
publisher = "Nature Publishing Group",
number = "18",
}